Single-cell multi-omics analysis reveals IFN-driven alterations in T lymphocytes and natural killer cells in systemic lupus erythematosus

Journal article

Background: The characterisation of the peripheral immune system in the autoimmune disease systemic lupus erythematosus (SLE) at the single-cell level has been limited by the reduced sensitivity of current whole-transcriptomic technologies. Here we employ a targeted single-cell multi-omics approach, combining protein and mRNA quantification, to generate a high-resolution map of the T lymphocyte and natural killer (NK) cell populations in blood from SLE patients.

Methods: We designed a custom panel to quantify the transcription of 534 genes in parallel with the expression of 51 surface protein targets using the BD Rhapsody AbSeq single-cell system. We applied this technology to profile 20,656 T and NK cells isolated from peripheral blood from an SLE patient with a type I interferon (IFN)-induced gene expression signature (IFN^hi), and an age- and sex- matched IFN^low SLE patient and healthy donor.

Results: We confirmed the presence of a rare cytotoxic CD4⁺ T cell (CTL) subset, which was exclusively present in the IFN^hi patient. Furthermore, we identified additional alterations consistent with increased immune activation in this patient, most notably a shift towards terminally differentiated CD57⁺ CD8⁺ T cell and CD16⁺ NK^dim phenotypes, and the presence of a subset of recently-activated naïve CD4⁺ T cells.

Conclusions: Our results identify IFN-driven changes in the composition and phenotype of T and NK cells that are consistent with a systemic immune activation within the IFN^hi patient, and underscore the added resolving power of this multi-omics approach to identify rare immune subsets. Consequently, we were able to find evidence for novel cellular peripheral biomarkers of SLE disease activity, including a subpopulation of CD57⁺ CD4⁺ CTLs.

Authors: Trzupek, D; Lee, M; Hamey, F; Wicker, LS; Todd, JA

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: F1000Research
• Journal: Wellcome Open Research
• Volume: 6
• Article number: 149
• Place of publication: England
• Publication date: 2021-06-14
• Acceptance date: 2022-05-16
• DOI: 10.12688/wellcomeopenres.16883.2
• EISSN: 2398-502X
• Pmid: 35509371
• Language: English
• Keywords: systemic lupus erythematosus (SLE); biomarker; FFR; cytotoxic CD4+ T cells (CTLs); AbSeq; BD Rhapsody; single-cell RNA-sequencing (scRNA-seq); multi-omics; type I interferon (IFN)